The subject matter of the invention is a mixing device and a method for the production of paste-like poly(methyl methacrylate) bone-cement pastes.
Conventional PMMA bone cements have been known for decades and trace back to the basic work done by Sir Charnley (Charnley, J.: “Anchorage of the femoral head prosthesis of the shaft of the femur,” J. Bone Joint Surg. 42: 28-30 (1960)). In principle, the basic formulation of the PMMA bone cements has remained the same since then. PMMA bone cements comprise a liquid monomer component and a powder component. The monomer component includes, in general, (i) the monomer methyl methacrylate and (ii) an activator (for example, N,N-dimethyl-p-toluidine) dissolved in this monomer. The powder component comprises (i) one or more polymers produced by polymerization, preferably suspension polymerization, on the basis of methyl methacrylate and comonomers, such as styrene, methyl acrylate, or similar monomers, (ii) a radiopaque material, and (iii) an initiator (for example, dibenzoyl peroxide). Upon mixing the powder component with the monomer component, a plastically deformable paste is produced due to swelling of the polymers of the powder component in the methyl methacrylate of the monomer component. Simultaneously, the activator N,N-dimethyl-p-toluidine reacts with the dibenzoyl peroxide, which breaks down with formation of radicals. The formed radicals initiate the radical polymerization of the methyl methacrylate. With advancing polymerization of the methyl methacrylate, the viscosity of the cement paste increases until the paste solidifies and is thus cured.
The significant disadvantage of the conventional PMMA bone cement for the medical user consists in that the user must mix the liquid monomer component with the powder component in a mixing system or crucibles directly before the application of the cement. Here, mixing errors can easily occur, which could negatively affect the cement quality. Furthermore, the mixing of the components must be performed in an uninterrupted process. Here, it is important that the entire cement powder is mixed with the monomer component without the formation of clumps and that, during the mixing process, the entry of air bubbles is avoided. With the use of vacuum mixing systems, in contrast to hand mixing, the formation of air bubbles in the cement paste is largely prevented. Examples of mixing systems are disclosed in the publications U.S. Pat. No. 4,015,945, European patent application publication EP 0 674 888 A1, and Japanese patent application publication (Kokai) JP 2003/181270 A. Vacuum mixing systems, however, make an additional vacuum pump necessary and are therefore relatively expensive. Furthermore, after the mixing of the monomer component with the powder component, depending on the type of cement, a certain amount of time must elapse until the cement paste is non-adhesive and can be applied. Due to the many possible errors in the mixing of conventional PMMA bone cements, appropriately trained personnel are also needed. The appropriate training is associated with considerable costs. Furthermore, the mixing of the liquid monomer component with the powder component leads to an exposure of the user to monomer vapors and to the release of powdery cement particles.
Paste-like bone cements represent an interesting alternative to conventional cements formulated from a powder component and a liquid component. Such paste-like bone cements are described, for example, in European patent application publications EP 2 052 747 A2 and EP 2 052 748 A2. Two-component paste cements are formulated from two storage-stable, paste-like components, which after mixing yield a cement paste that cures within a few minutes. These pastes are made available to the medical user in cartridges or in tubular bags. These bone-cement pastes contain at least (i) a monomer, (ii) a polymer soluble in this monomer, and (iii) a polymer insoluble in this monomer and/or other fillers. In addition, components of redox initiator systems are contained in the cement pastes. Furthermore, it is also possible to produce single-component-paste bone cements which, in contrast to two-component systems, are brought to polymerization by action of energy, for example by changing magnetic fields.
For the production of these cement pastes, a powder-like cement component A and a liquid monomer component B are mixed. The powder-like component A comprises a polymer soluble in the monomers of the monomer component B, a polymer insoluble in the monomers of the monomer component B and/or fillers. Upon mixing of the powder-like cement component A with the liquid monomer component B, the polymer soluble in the monomer or monomer mixture swells, before it then dissolves in the monomer/monomer mixture. The viscosity of the mixture here increases greatly, so that the mixture forms a paste. The viscosity of the paste is so high that the insoluble polymer and/or the fillers do not settle out. With the use of quickly swelling, soluble polymers, this process takes place within 5-30 minutes. During this swelling phase, it is necessary to stir or to knead the mixture, so that no phase separation can take place through sedimentation. Thereafter, the soluble polymer swells only to a slight extent.
The production of pastes is a typical process in the food and adhesive industries, which is performed with the help of large-volume mixing vessels. Here, at least one mixing of the paste components is performed with conventional blade or rod stirrers. The formed pastes are pressed out from the mixing vessels through fitted movable covers with the help of presses into suitable packaging means, such as cartridges, tubular bags, and tubes. The degassing of the formed paste-like materials, however, is problematic due to their viscosity that is, in part, very high.
The monomer mainly contained in bone-cement pastes, methyl methacrylate, involves a very reactive and volatile liquid. Besides methyl methacrylate, dissolved polymers, as for example poly(methyl methacrylate), are also contained in the bone-cement pastes. Upon mixing of the poly(methyl methacrylate) with the methyl methacrylate, a gel is formed. Therefore, cement pastes are in a gel-like state. The monomer mixtures contained in the cement pastes are then already extremely reactive when the cement paste is in a gel-like state. Consequently, these systems have a certain tendency for spontaneous polymerization.
In radical polymerization methyl methacrylate releases an enthalpy of reaction of −59 kJ/mol. Typical preparation containers have a holding capacity of ca. 200 liters. At the start of paste cement of ca. 200 kg, which contains ca. 40 weight percent monomer, ca. 80 kg (corresponding to 800 mol) of methyl methacrylate is included. With an undesired spontaneous polymerization of these starting materials, an energy of approximately −47,200 kJ would be released within a few minutes, which could lead to a conflagration or to an explosion. Furthermore, after spontaneous polymerization of the cement paste, the very expensive preparation containers are no longer usable, because the cured bone-cement pastes are mechanically very resistant. Therefore, the use of conventional preparation containers for the production of bone-cement pastes is very problematic. Furthermore, the degassing of the formed cement paste has also proven to be problematic. Air residues enclosed in the cement pastes can, on one hand, negatively affect the storage capacity of the pastes due to the included oxygen and, on the other hand, air inclusions can degrade the mechanical stability of the cured cement.